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| ID | Type | Description | Link |
|---|---|---|---|
| 3000-01-003 | Other Identifier | Tesaro |
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Niraparib (Zejula®)is extensively metabolized and eliminated primarily by hepatic and renal pathways. The purpose of this study is to evaluate pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment, for the purpose of providing recommendations to guide the initial dose and dose titration in this patient population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal hepatic function (Group 1): | Experimental | To evaluate the pharmocokinetics and safety of niraparib |
|
| Moderate hepatic impairment (Group 2): | Experimental | To evaluate the pharmocokinetics and safety of niraparib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Niraparib | Drug | Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Niraparib and Its Major Metabolite (M1) During PK Phase | Blood samples were collected at indicated time points to evaluate AUC (last) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
| Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate AUC (0-infinity) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
| Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate Cmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
| Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate tmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
| Terminal Half-life (t½) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate t1/2 of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAE) Including Non-serious Adverse Events (Non-SAEs), Serious Adverse Events (SAEs) and Discontinuations Due to AEs During PK Phase | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Protein Unbound Fraction (Fu) of Niraparib and M1 During PK Phase | Unbound fraction is the unbound concentration of niraparib and M1 in plasma divided by total concentration. This analysis was planned but not performed due to insufficient participants with data | Pre-dose, 3 hours and 168 hours post dose Day 1 |
Inclusion Criteria:
Diagnosis and Criteria for Inclusion:
All patients:
To be considered eligible to participate in this study, all of the following requirements must be met:
Patient, male or female, is at least 18 years of age.
Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Patient is able to take oral medications.
Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
Patients with normal hepatic function (Group 1):
Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:
Patient has no history of hepatic impairment.
Patient has liver function test (LFT) results within normal range:
Patient has adequate hematologic and renal function as defined below:
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:
Patient has stable, moderate hepatic impairment, defined as:
Patient has hematologic and renal function as defined below:
Patient's hepatic disease is deemed stable by the Investigator
Criteria for Exclusion:
Patients will not be eligible for study entry if any of the following criteria are met:
All patients:
Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing >20% of the bone marrow.
Patient is starting chemotherapy within 3 weeks of study drug administration.
Patient has a known hypersensitivity to the components of niraparib or excipients
Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible.
Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue.
Patient has symptomatic uncontrolled brain or leptomeningeal metastases.
Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection.
Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib.
Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment.
Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
NOTE: Exclusion Criteria 12-16 apply patients participating in the PK phase of the study.
Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the time of the last PK blood draw, any of the following cytochrome (CYP) 1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and theophylline.
Patient is unable to refrain from any intake of grapefruit or grapefruit juice within 4 days of the first administration of niraparib until the final PK sample collection.
Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the last PK blood draw, any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor and verapamil.
Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers within 48 hours prior to niraparib administration, and/or within 6 hours after niraparib administration.
Patient has esophagogastrointestinal disease or resection that is likely to interfere with the absorption of niraparib.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group who meet any of the following additional criteria will be excluded from the study:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Los Angeles | California | 90033 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34324028 | Derived | Akce M, El-Khoueiry A, Piha-Paul SA, Bacque E, Pan P, Zhang ZY, Ewesuedo R, Gupta D, Tang Y, Milton A, Zajic S, Judson PL, O'Bryant CL. Pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment. Cancer Chemother Pharmacol. 2021 Nov;88(5):825-836. doi: 10.1007/s00280-021-04329-8. Epub 2021 Jul 29. |
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This is a 2 period study including pharmacokinetic (PK) phase and extension (Ext.) phase. A total of 17 participants were enrolled in the study and received study treatment, niraparib.
This study evaluated pharmacokinetics and safety of niraparib in participants with advanced solid tumors and with either normal hepatic function or moderate hepatic impairment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants With Normal Hepatic Function | All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). |
| FG001 | Participants With Impaired Hepatic Function | All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PK Phase (Up to Day 8) |
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| |||||||||||||||||||||
| Extension Phase (Up to 28 Months) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants With Normal Hepatic Function | All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Safety Population consisted of all participants who received drug |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Niraparib and Its Major Metabolite (M1) During PK Phase | Blood samples were collected at indicated time points to evaluate AUC (last) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | PK population consisted of all participants who have received niraparib and have sufficient evaluable samples | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter (hr*ng/mL) | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
|
All cause mortality, non-SAEs and SAEs were reported from start of study treatment and up to Day 8 in PK Phase and up to 28 months in Extension Phase.
All cause mortality, non-SAEs and SAEs were reported for Safety Population consisting of all participants who received atleast 1 dose of the investigational drug, niraparib. The results are presented based on final analysis up to 28 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants With Normal Hepatic Function-PK Phase | All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 15, 2018 | Aug 18, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 31, 2020 | Aug 18, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
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| ID | Term |
|---|---|
| C545685 | niraparib |
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| Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase | CL/F is calculated as Dose/(AUC 0-inf). Blood samples were collected at indicated time points to evaluate CL/F of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates that CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib. | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
| Up to Day 8 |
| Change From Baseline in Hemoglobin (Hb) During PK Phase | Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and at Day 8 |
| Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Blood samples were collected to analyze hematology parameters:Leukocyte, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and Day 8 |
| Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase | Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and Day 8 |
| Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and Day 8 |
| Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and Day 8 |
| Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and Day 8 |
| Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline and Day 8 |
| Change From Baseline in Weight During PK Phase | Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline, Day 2 and Day 8 |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline, Day 2 and Day 8 |
| Change From Baseline in Pulse Rate During PK Phase | Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline, Day 2 and Day 8 |
| Change From Baseline in Body Temperature During PK Phase | Vital sign including body temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Baseline, Day 2 and Day 8 |
| Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. | Up to 28 months |
| Change From Baseline in Hb During Extension Phase | Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Blood samples were collected to analyze hematology parameters: Lymphocytes, Leukocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Weight During Extension Phase | Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in SBP and DBP During Extension Phase | Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Pulse Rate During Extension Phase | Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Change From Baseline in Temperature During Extension Phase | Vital sign including temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
| Clearance of Unbound Niraparib and M1 (CLfu/F) During PK Phase |
CLfu/F is the clearance for unbound niraparib and M1. This analysis was planned but not performed due to insufficient participants with data |
| Pre-dose, 3 hours and 168 hours post dose Day 1 |
| Newport Beach |
| California |
| 92663 |
| United States |
| GSK Investigational Site | Aurora | Colorado | 80045 | United States |
| GSK Investigational Site | Atlanta | Georgia | 30322 | United States |
| GSK Investigational Site | Houston | Texas | 77030 | United States |
| NOT COMPLETED |
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| BG001 | Participants With Impaired Hepatic Function | All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | Participants With Impaired Hepatic Function | All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). |
|
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| Primary | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate AUC (0-infinity) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | PK population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter (hr*ng/mL) | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
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| Primary | Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate Cmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
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| Primary | Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate tmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | PK population | Posted | Median | Full Range | Hour | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
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| Primary | Terminal Half-life (t½) of Niraparib and M1 During PK Phase | Blood samples were collected at indicated time points to evaluate t1/2 of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. | PK population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
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|
| Primary | Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase | CL/F is calculated as Dose/(AUC 0-inf). Blood samples were collected at indicated time points to evaluate CL/F of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates that CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib. | PK population. Only those participants with data available at specified data points were analyzed. CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1 |
|
|
|
| Other Pre-specified | Plasma Protein Unbound Fraction (Fu) of Niraparib and M1 During PK Phase | Unbound fraction is the unbound concentration of niraparib and M1 in plasma divided by total concentration. This analysis was planned but not performed due to insufficient participants with data | PK population. | Posted | Pre-dose, 3 hours and 168 hours post dose Day 1 |
|
|
| Other Pre-specified | Clearance of Unbound Niraparib and M1 (CLfu/F) During PK Phase | CLfu/F is the clearance for unbound niraparib and M1. This analysis was planned but not performed due to insufficient participants with data | PK population. | Posted | Pre-dose, 3 hours and 168 hours post dose Day 1 |
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAE) Including Non-serious Adverse Events (Non-SAEs), Serious Adverse Events (SAEs) and Discontinuations Due to AEs During PK Phase | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. | Safety Population for PK phase consisted of all participants who received atleast one dose of the investigational drug niraparib during the PK phase. | Posted | Count of Participants | Participants | Up to Day 8 |
|
|
|
| Secondary | Change From Baseline in Hemoglobin (Hb) During PK Phase | Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed. | Posted | Mean | Standard Deviation | Grams per liter | Baseline and at Day 8 |
|
|
|
| Secondary | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase | Blood samples were collected to analyze hematology parameters:Leukocyte, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline and Day 8 |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase | Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed. | Posted | Mean | Standard Deviation | Grams per liter | Baseline and Day 8 |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed. | Posted | Mean | Standard Deviation | International units per Liter | Baseline and Day 8 |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed. | Posted | Mean | Standard Deviation | Units per Liter | Baseline and Day 8 |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline and Day 8 |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Millimoles per liter | Baseline and Day 8 |
|
|
|
| Secondary | Change From Baseline in Weight During PK Phase | Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Kilograms | Baseline, Day 2 and Day 8 |
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|
|
| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase | Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline, Day 2 and Day 8 |
|
|
|
| Secondary | Change From Baseline in Pulse Rate During PK Phase | Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Beats per minute | Baseline, Day 2 and Day 8 |
|
|
|
| Secondary | Change From Baseline in Body Temperature During PK Phase | Vital sign including body temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline, Day 2 and Day 8 |
|
|
|
| Secondary | Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. | Safety Population for extension phase consisted of all participants who received atleast one dose of the investigational drug niraparib during the extension phase. | Posted | Count of Participants | Participants | Up to 28 months |
|
|
|
| Secondary | Change From Baseline in Hb During Extension Phase | Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Grams per liter | Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase | Blood samples were collected to analyze hematology parameters: Lymphocytes, Leukocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase | Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Grams per liter | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | International units per Liter | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Units per Liter | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase | Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Millimoles per liter | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Weight During Extension Phase | Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Kilograms | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in SBP and DBP During Extension Phase | Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Pulse Rate During Extension Phase | Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Beats per minute | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| Secondary | Change From Baseline in Temperature During Extension Phase | Vital sign including temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days) |
|
|
|
| 0 |
| 9 |
| 1 |
| 9 |
| 5 |
| 9 |
| EG001 | Participants With Impaired Hepatic Function-PK Phase | All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). | 0 | 8 | 0 | 8 | 3 | 8 |
| EG002 | Participants With Normal Hepatic Function-Extension Phase | All participants received a single dose of 300 milligrams (mg) (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants with screening actual body weight >= 77 kilograms (kg) and current platelet count of >=150,000 cells per microliter (c/μL) at C1D1 continued to receive niraparib 300 mg/day (3X100 mg) once daily (QD) on Day 1 of every cycle until treatment discontinuation(each cycle of 28-days). Participants with screening actual body weight < 77 kg and/or current platelet count of <150,000 c/μL continued to receive niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). | 2 | 8 | 3 | 8 | 8 | 8 |
| EG003 | Participants With Impaired Hepatic Function-Extension Phase | All participants received a single dose of 300 mg (3X100 mg capsules) niraparib administered on Day 1 of PK phase. Upon entering extension phase, participants received niraparib 200 mg (2X100 mg capsules) QD on Day 1 of every cycle until treatment discontinuation (each cycle of 28 days). | 4 | 7 | 2 | 7 | 7 | 7 |
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ventricular tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D005831 |
| Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| M1, n=9, 3 |
|
|
| M1, n=9, 3 |
|
|
| Any Discontinuations due to AE |
|
| Neutrophils |
|
| Platelets |
|
| Leukocyte |
|
| ALT |
|
| LDH |
|
| Calcium, n=8, 8 |
|
|
| Chloride, n=8, 8 |
|
|
| Phosphate, n=8, 8 |
|
|
| Potassium, n=8, 8 |
|
|
| Sodium, n=8, 8 |
|
|
| BUN, n=8, 8 |
|
|
| Magnesium, n=8, 7 |
|
|
| Day 8, n=9, 8 |
|
|
| SBP, Day 8, n=9, 8 |
|
|
| DBP, Day 2, n=9, 7 |
|
|
| DBP, Day 8, n=9, 8 |
|
|
| Day 8, n=9, 8 |
|
|
| Day 8, n=9, 8 |
|
|
| Any Discontinuations due to AE |
|
| Cycle 1 Day 15, n=8, 4 |
|
|
| Cycle 1 Day 21, n=7, 4 |
|
|
| Cycle 2 Day 1, n=6, 2 |
|
|
| Cycle 3 Day 1, n=3, 1 |
|
|
| Cycle 4 Day 1, n=3, 0 |
|
|
| Cycle 5 Day 1, n=3, 0 |
|
|
| Cycle 6 Day1, n=2, 0 |
|
|
| Lymphocytes, Cycle 1 Day 15, n=8, 4 |
|
|
| Lymphocytes, Cycle 1 Day 21, n=7, 4 |
|
|
| Lymphocytes, Cycle 2 Day 1, n=6, 2 |
|
|
| Lymphocytes, Cycle 3 Day 1, n=3, 1 |
|
|
| Lymphocytes, Cycle 4 Day 1, n=3, 0 |
|
|
| Lymphocytes, Cycle 5 Day 1, n=3, 0 |
|
|
| Lymphocytes, Cycle 6 Day1, n=2, 0 |
|
|
| Monocytes, Cycle 1 Day 8, n=7, 5 |
|
|
| Monocytes, Cycle 1 Day 15, n=8, 4 |
|
|
| Monocytes, Cycle 1 Day 21, n=7, 4 |
|
|
| Monocytes, Cycle 2 Day 1, n=6, 2 |
|
|
| Monocytes, Cycle 3 Day 1, n=3, 1 |
|
|
| Monocytes, Cycle 4 Day 1, n=3, 0 |
|
|
| Monocytes, Cycle 5 Day 1, n=3, 0 |
|
|
| Monocytes, Cycle 6 Day1, n=2, 0 |
|
|
| Neutrophils, Cycle 1 Day 8, n=7, 5 |
|
|
| Neutrophils, Cycle 1 Day 15, n=8, 4 |
|
|
| Neutrophils, Cycle 1 Day 21, n=7, 4 |
|
|
| Neutrophils, Cycle 2 Day 1, n=6, 2 |
|
|
| Neutrophils, Cycle 3 Day 1, n=3, 1 |
|
|
| Neutrophils, Cycle 4 Day 1, n=3, 0 |
|
|
| Neutrophils, Cycle 5 Day 1, n=3, 0 |
|
|
| Neutrophils, Cycle 6 Day1, n=2, 0 |
|
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| Platelets, Cycle 1 Day 8, n=8, 5 |
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| Platelets, Cycle 1 Day 15, n=8, 4 |
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| Platelets, Cycle 1 Day 21, n=7, 4 |
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| Platelets, Cycle 2 Day 1, n=6, 2 |
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| Platelets, Cycle 3 Day 1, n=3, 1 |
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| Platelets, Cycle 4 Day 1, n=3, 0 |
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| Platelets, Cycle 5 Day 1, n=3, 0 |
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| Platelets, Cycle 6 Day1, n=2, 0 |
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| Leukocytes, Cycle 1 Day 8, n=8, 5 |
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| Leukocytes, Cycle 1 Day 15, n=8, 4 |
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| Leukocytes, Cycle 1 Day 21, n=7, 4 |
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| Leukocytes, Cycle 2 Day 1, n=6, 2 |
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| Leukocytes, Cycle 3 Day 1, n=3, 1 |
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| Leukocytes, Cycle 4 Day 1, n=3, 0 |
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| Leukocytes, Cycle 5 Day 1, n=3, 0 |
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| Leukocytes, Cycle 6 Day1, n=2, 0 |
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| Protein, Cycle 3 Day 1, n=3, 1 |
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| Protein, Cycle 4 Day 1, n=3, 0 |
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| Protein, Cycle 5 Day 1, n=3, 0 |
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| Protein, Cycle 6 Day1, n=2, 0 |
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| Albumin, Cycle 2 Day 1, n=6, 2 |
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| Albumin, Cycle 3 Day 1, n=3, 1 |
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| Albumin, Cycle 4 Day 1, n=3, 0 |
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| Albumin, Cycle 5 Day 1, n=3, 0 |
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| Albumin, Cycle 6 Day1, n=2, 0 |
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| Alkaline Phosphatase, Cycle 3 Day 1, n=3, 1 |
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| Alkaline Phosphatase, Cycle 4 Day 1, n=3, 0 |
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| Alkaline Phosphatase, Cycle 5 Day 1, n=3, 0 |
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| Alkaline Phosphatase, Cycle 6 Day1, n=2, 0 |
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| ALT, Cycle 2 Day 1, n=6, 2 |
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| ALT, Cycle 3 Day 1, n=3, 1 |
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| ALT, Cycle 4 Day 1, n=3, 0 |
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| ALT, Cycle 5 Day 1, n=3, 0 |
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| ALT, Cycle 6 Day1, n=2, 0 |
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| AST, Cycle 2 Day 1, n=6, 2 |
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| AST, Cycle 3 Day 1, n=3, 1 |
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| AST, Cycle 4 Day 1, n=3, 0 |
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| AST, Cycle 5 Day 1, n=3, 0 |
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| AST, Cycle 6 Day1, n=2, 0 |
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| LDH, Cycle 2 Day 1, n=3, 2 |
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| LDH, Cycle 3 Day 1, n=3, 1 |
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| LDH, Cycle 4 Day 1, n=3, 0 |
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| LDH, Cycle 5 Day 1, n=3, 0 |
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| LDH, Cycle 6 Day1, n=2, 0 |
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| Cycle 3 Day 1, n=3, 1 |
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| Cycle 4 Day 1, n=3, 0 |
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| Cycle 5 Day 1, n=3, 0 |
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| Cycle 6 Day1, n=2, 0 |
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| Bilirubin, Cycle 3 Day 1, n=3, 1 |
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| Bilirubin, Cycle 4 Day 1, n=3, 0 |
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| Bilirubin, Cycle 5 Day 1, n=3, 0 |
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| Bilirubin, Cycle 6 Day1, n=2, 0 |
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| Creatinine, Cycle 2 Day 1, n=6, 2 |
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| Creatinine, Cycle 3 Day 1, n=3, 1 |
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| Creatinine, Cycle 4 Day 1, n=3, 0 |
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| Creatinine, Cycle 5 Day 1, n=3, 0 |
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| Creatinine, Cycle 6 Day1, n=2, 0 |
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| Glucose, Cycle 3 Day 1, n=3, 1 |
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| Glucose, Cycle 4 Day 1, n=3, 0 |
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| Glucose, Cycle 5 Day 1, n=3, 0 |
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| Glucose, Cycle 6 Day1, n=2, 0 |
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| Calcium, Cycle 2 Day 1, n=6, 2 |
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| Calcium, Cycle 3 Day 1, n=3, 1 |
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| Calcium, Cycle 4 Day 1, n=3, 0 |
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| Calcium, Cycle 5 Day 1, n=3, 0 |
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| Calcium, Cycle 6 Day1, n=2, 0 |
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| Chloride, Cycle 2 Day 1, n=6, 2 |
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| Chloride, Cycle 3 Day 1, n=3, 1 |
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| Chloride, Cycle 4 Day 1, n=3, 0 |
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| Chloride, Cycle 5 Day 1, n=3, 0 |
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| Chloride, Cycle 6 Day1, n=2, 0 |
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| Phosphate, Cycle 2 Day 1, n=5, 2 |
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| Phosphate, Cycle 3 Day 1, n=3, 1 |
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| Phosphate, Cycle 4 Day 1, n=3, 0 |
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| Phosphate, Cycle 5 Day 1, n=3, 0 |
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| Phosphate, Cycle 6 Day1, n=2, 0 |
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| Potassium, Cycle 2 Day 1, n=6, 2 |
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| Potassium, Cycle 3 Day 1, n=3, 1 |
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| Potassium, Cycle 4 Day 1, n=3, 0 |
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| Potassium, Cycle 5 Day 1, n=3, 0 |
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| Potassium, Cycle 6 Day1, n=2, 0 |
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| Sodium, Cycle 2 Day 1, n=6, 2 |
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| Sodium, Cycle 3 Day 1, n=3, 1 |
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| Sodium, Cycle 4 Day 1, n=3, 0 |
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| Sodium, Cycle 5 Day 1, n=3, 0 |
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| Sodium, Cycle 6 Day1, n=2, 0 |
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| BUN, Cycle 2 Day 1, n=6, 2 |
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| BUN, Cycle 3 Day 1, n=3, 1 |
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| BUN, Cycle 4 Day 1, n=3, 0 |
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| BUN, Cycle 5 Day 1, n=3, 0 |
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| BUN, Cycle 6 Day1, n=2, 0 |
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| Magnesium, Cycle 2 Day 1, n=5, 2 |
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| Magnesium, Cycle 3 Day 1, n=3, 1 |
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| Magnesium, Cycle 4 Day 1, n=2, 0 |
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| Magnesium, Cycle 5 Day 1, n=2, 0 |
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| Magnesium, Cycle 6 Day1, n=1, 0 |
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| Cycle 3 Day 1, n=3, 1 |
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| Cycle 4 Day 1, n=3, 0 |
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| Cycle 5 Day 1, n=3, 0 |
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| Cycle 6 Day1, n=2, 0 |
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| DBP, Cycle 3 Day 1, n=3, 1 |
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| DBP, Cycle 4 Day 1, n=3, 0 |
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| DBP, Cycle 5 Day 1, n=3, 0 |
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| DBP, Cycle 6 Day1, n=2, 0 |
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| SBP, Cycle 2 Day 1, n=6, 2 |
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| SBP, Cycle 3 Day 1, n=3, 1 |
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| SBP, Cycle 4 Day 1, n=3, 0 |
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| SBP, Cycle 5 Day 1, n=3, 0 |
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| SBP, Cycle 6 Day1, n=2, 0 |
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| Cycle 3 Day 1, n=3, 1 |
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| Cycle 4 Day 1, n=3, 0 |
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| Cycle 5 Day 1, n=3, 0 |
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| Cycle 6 Day1, n=2, 0 |
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| Cycle 3 Day 1, n=3, 1 |
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| Cycle 4 Day 1, n=3, 0 |
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| Cycle 5 Day 1, n=3, 0 |
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| Cycle 6 Day1, n=2, 0 |
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